October 26, 2012
(The New York Times News Service) -- Inside its sprawling red brick offices, New England Compounding Center engaged in the most hazardous type of pharmacy drug making. The company bought unsterilized powders and turned them into liquid steroids and other medicine supposedly pristine enough to inject into a patient.
It's called "high-risk compounding," and doing this safely, industry specialists say, requires elaborate and expensive manufacturing processes, sensitive tests for sterility and potency, and exacting attention to detail.
At the center of the federal and state investigation into New England Compounding, whose steroids were contaminated with a fungus that led to an outbreak of meningitis that has killed 24 people nationally, is whether the company violated these procedures.
Injectable drugs made from raw ingredients are so susceptible to contamination that in 2009 the Food and Drug Administration highlighted them on a list of medicines that are especially risky for pharmacies to prepare.
The agency offered that list as "guidance to industry," but did not have authority to enforce rules to ensure that pharmacies follow proper practices, FDA spokesman Steven Immergut said last week.
Andrew Paven, a spokesman for New England Compounding, said the company did make drugs from bulk raw materials, but that the approach is typical of the compounding industry.
Findings released Tuesday by the state Department of Public Health show that the company ignored state regulations requiring sterility testing for these medicines to be completed before sending them to doctors and patients. On 13 occasions, New England Compounding shipped vials of methylprednisolone acetate from two of the three contaminated lots prior to receiving test results on samples, in one case mailing the drug almost two weeks before results came in.
The pharmacy's records show that test results for the steroid eventually showed no contamination, which the Public Health Department said raises questions about the adequacy of the testing.
Compounders are required to have a minimum number of samples from each batch of high-risk medications tested for bacteria and fungi if the refrigerated drugs will be used by patients more than three days after they are made, said Eric Kastango, a New Jersey-based pharmacist and safety consultant to the industry. Portions of the samples are Âincubated to see whether bacteria or fungi grow.
But Kastango said it is possible that the fungus was so slow-growing that it did not show up in the steroid samples, that the test was not sensitive enough, that too few samples were tested, or that there was some other problem with the testing. State officials said Thursday they could not provide more details, including how many samples were tested. Industry specialists said that for lots the size of the three tainted steroid batches, at least 20 vials should be tested to ensure that contaminants are caught.
New England Compounding inspection reports dating back a decade show that it said it followed the rules. The company told state inspectors in 2002 that the steroid was "released from quarantine only after the sample had tested negative for microbial contamination," which typically took seven to 10 days, according to state records.
Kastango said compounders have often jumped the gun on testing, which is inconvenient and time-consuming.
"The demand [for drugs] was so high, they felt if they haven't had a problem in the past, everything was fine and so they decided to go ahead and do it," Kastango said. "A lot of people got overconfident in their process."
Since the meningitis outbreak, compounders don't feel they can "take the risk anymore" and are waiting for test results, he added.
Testing is a safeguard, but sterile procedures at New England Compounding should have been thorough enough to prevent contamination in the first place, Kastango said.
To do high-risk compounding right, pharmacies spend as much as $2 million to create germ-proof areas like operating rooms. Pharmacists and technicians are supposed to scrub in like surgeons and constantly test the air and equipment to make sure these precautions are keeping out fungi and bacteria, he said. But in the case of New England Compounding, state investigators found the company did not sterilize the steroid for the minimum 20 minutes required and did not test autoclaves, which sterilize items using steam at high pressure.
This "is not a light undertaking," said David G. Miller, executive vice president of the International Academy of Compounding Pharmacists. "It requires much more attention to detail. I know whatever I produce is going straight into someone's body."
Compounding pharmacies make drugs from raw materials if they are unable to buy a ready-made mixture from an FDA-approved supplier, pharmacists said, or if patients are allergic to an ingredient in off-the-shelf medications or because it's more profitable.
In the case of the contaminated steroid made by New England Compounding, preservative-free methylprednisolone acetate, doctors prefer to use the drug without an alcohol-based preservative for pain injections near the spine because of concerns that alcohol can damage nerves. The medication had to be made from raw ingredients because the only ready-made solutions available on the market contain preservatives, said Sarah Sellers, a Chicago-based pharmacy safety consultant and former FDA adviser.
In 2009, the FDA said compounding sterile products from nonsterile ingredients is risky in part because some compounders assume that filtering removes bacteria when "sterilizing grade filters may not consistently remove all harmful foreign substances that may be present in nonsterile ingredients."
Sellers said compounders may not know where a chemical originated and could be using raw pharmaceutical ingredients made overseas in factories not approved by the FDA.
The agency has also warned about the risk of contamination when compounding pharmacies break open the packaging of sterile drugs and repackage them to sell to doctors, a process normally considered relatively low risk. In 2006, the agency warned New England Compounding about splitting Avastin and repackaging it into smaller doses. This has been done to treat macular degeneration and avoid using the similar, more expensive drug approved for that purpose, Lucentis.
"The moment a sterile container is opened and manipulated, quality standard [sterility] is destroyed and previous studies supporting the standard are compromised and no longer valid," the agency wrote.
Copyright 2012 The New York Times News Service. All rights reserved.